Homeostatic tuning of Ca2+ signal transduction by members of the calpacitin protein family

Abstract

The calpacitin protein family is made up of small, abundantly expressed proteins that bind to the Ca(2+)-free form of calmodulin (CaM) with an affinity equal to or greater than that of the Ca(2+)-containing form. Their CaM-binding domains are homologous and contain an IQ motif. Two members of this family, growth-associated protein-43 (GAP-43) and RC3, have been implicated in long-term potentiation (LTP) and the elaboration of pre- and postsynaptic structures. Computer-aided modeling of calpacitin-CaM interactions suggests that these molecules regulate Ca2+ flux size and CaM availability. Simulation of the interactions between the calpacitins CaM and Ca2+ imply that GAP-43 and RC3 tune and homeostatically constrain the Ca2+ signal transduction system. In so doing, they link Ca2+ fluxes to downstream elements of a signaling cascade that generates LTP.